Zhouguang Hui, Abstract Co-Author: Nothing to Disclose

Xiaozhen Wang MD, PhD, Presenter: Nothing to Disclose

Zhong-Fa Zhang, Abstract Co-Author: Nothing to Disclose

David Petillo, Abstract Co-Author: Nothing to Disclose

Yuanhong Gao MD, PhD, Abstract Co-Author: Nothing to Disclose

Julie Zhu, Abstract Co-Author: Nothing to Disclose

Weiyuan Mai MD, Abstract Co-Author: Nothing to Disclose

Brian Butler, Abstract Co-Author: Nothing to Disclose

Bin Tean Teh, Abstract Co-Author: Nothing to Disclose

Bin Sing Teh MD, Abstract Co-Author: Nothing to Disclose

et al, Abstract Co-Author: Nothing to Disclose

RCC is a radio-resistant malignancy. The molecular basis for radio-resistance in RCC is not well understood. The purpose of this study to analyze the gene expression profiling after irradiation is the first step in exploring the molecular mechanism of radio-resistance in RCC.

Four different comparisons were designed: 1: Cell line track. Four RCC cell lines (CRL1932, CRL1611, SN12C and HTB44) were irradiated with 4Gy respectively. Total RNA was extracted prior to, 2 and 72 hours after irradiation (IR). 2: Time track. CRL1611 was irradiated with 2Gy. Total RNA was extracted prior to, 2, 6, 12, 24, 48 and 72 hours after IR. 3: Dosage track. CRL 1611 was irradiated with 0.5, 2, 5, 10 and 20Gy. Total RNA was extracted prior to and 2 hours after IR. 4: Fractionation track. CRL1932 was irradiated with 2Gy fraction per day for 5 continuous days or 10Gy single dose fraction. Total RNA was extracted prior to and 24 hours after IR. The Affymetrix HGU133 Plus 2.0 GeneChip oligonucleotide arrays were used.

Comparison 1: When using cutoff point of 0.75-1.5, the numbers of total gene changed after IR for the four cell lines were different. The numbers of overlapping (common) changed gene were: 395 up- and 303 down- regulated (2 hours) and 289 up- and 222 down-regulated (72 hours). There were 112 common genes up-regulated and 85 common genes down-regulated both in 2 hours and 72 hours after IR.Comparison 2: After different times of IR, the peak changes occurred at 12 hours after IR. There were almost no changes at 2 hours (latent period). After 12 hours, there were a small proportion of genes returning to normal baseline. However, a significant number of genes changed at 12 hours persisted after that period. More genes were noted to be down regulated than up-regulated.Comparison 3: In contrast to the above, more genes were up-regulated than down-regulated. When using cut-off point of 2 and 4, 30-80 and 2-5 genes changes were observed. The least and most changes were observed in 2 and 20Gy of IR respectively. There were slightly more gene changes with 0.5 Gy compared to 2Gy of IR, may be due to low-dose radiation hypersensitivity.Comparison 4: Using the cut-off point of 3, there were 42 and 66 genes changed in the conventional fractionation schema (2Gy times 5 fractions) and stereotactic fractionation schema (10Gy single fraction) respectively. 31 common genes changed were noted in both schemas.

Different gene change modes were observed after different comparison tracks (cell lines, time, dosage and fractionation) of IR in RCC. There were many gene changes in common. Further identification of specific gene(s) and function(s) is beneficial for elucidating radio-resistance and may serve as targets for radio-sensitization. Cellular pathway exploration studies are in progress.

Hui, Z, Wang, X, Zhang, Z, Petillo, D, Gao, Y, Zhu, J, Mai, W, Butler, B, Teh, B, Teh, B, et al, , Gene Expression Profiling after Irradiation in Radio-resistant Human Renal Cell Carcinoma (RCC).  Radiological Society of North America 2008 Scientific Assembly and Annual Meeting, February 18 - February 20, 2008 ,Chicago IL. http://archive.rsna.org/2008/7001086.html